Biochemical and molecular processes related to initiation and progression of the atherosclerotic lesion have yet to be fully defined. This SCOR program is an interdisciplinary approach to the study of thrombotic disease and angiogenesis as it relates to atherogenesis. How these processes relate at the cellular and molecular level will be a significant theme of the program. Our investigation will include a genetic engineering approach employing several animal models of the disease (mouse CD36 and apo E knockout models, rat angioplasty model, and the rabbit atherosclerosis model) to address: scavenger receptors in foam cell development, fibrinolytic factors and tissue-remodeling in angiogenesis, mitogenic factors in the formation of the coronary network and patterning of coronary vessels, and the molecular deficiencies associated with growth control of atherosclerotic cells using dominant-negative constructs to specific growth factor receptor genes. To address these objectives, a Molecular Biology/Gene Transfer Core has been constructed to facilitate investigations involving gene transfer, gene regulation, and maintenance of the genetically-modified animal models. In addition, a gene therapy approach will be used to develop clinical strategies for the induction of angiogenesis. Emphasis has also been placed on the use of clinical samples consisting of human atherosclerotic and restenotic tissues. These materials will be studies in an effort to extend the paradigms resulting from the use of genetically modified animal models to advance our understanding of human lesion progression. Our SCOR program has been crafted to capitalize on the complimentary research expertise of our cardiovascular biology group at Cornell. Together, our synergistic efforts have culminated in over 100 peer-reviewed, basic research papers in the past 5 years, underscoring the success of our scientific collaborations. As a testament to our achievements, Cornell Medical School has recently developed a new Center of Vascular Biology, headed by Dr. David Hajjar. Committed institutional funds (greater than $1.0 million) are earmarked for modern capital improvements to include renovations of laboratories, the purchase of new equipment, and for faculty recruitment.